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Molecular classification of human cancers using a 92-gene real-time quantitative polymerase chain reaction assay.

Abstract：

CONTEXT:Correct diagnosis of the tissue origin of a metastatic cancer is the first step in disease management, but it is frequently difficult using standard pathologic methods. Microarray-based gene expression profiling has shown great promise as a new tool to address this challenge. OBJECTIVE:Adoption of microarray technologies in the clinic remains limited. We aimed to bridge this technological gap by developing a real-time quantitative polymerase chain reaction (RT-PCR) assay. DESIGN:We constructed a microarray database of 466 frozen and 112 formalin-fixed, paraffin-embedded (FFPE) samples of both primary and metastatic tumors, measuring expression of 22,000 genes. From the microarray database, we used a genetic algorithm to search for gene combinations optimal for multitumor classification. A 92-gene RT-PCR assay was then designed and used to generate a database for 481 frozen and 119 FFPE tumor samples. RESULTS:The microarray-based K-nearest neighbor classifier demonstrated 84% accuracy in classifying 39 tumor types via cross-validation and 82% accuracy in predicting 112 independent FFPE samples. We successfully translated the microarray database to the RT-PCR platform, which allowed an overall success rate of 87% in classifying 32 different tumor classes in the validation set of 119 FFPE tumor samples. CONCLUSIONS:The RT-PCR-based expression assay involving 92 genes represents a powerful tool for accurately and objectively identifying the site of origin for metastatic tumors, especially in the cases of cancer of unknown primary. The assay uses RT-PCR and routine FFPE samples, making it suitable for rapid clinical adoption.

journal_name

Arch Pathol Lab Med

journal_title

Archives of pathology & laboratory medicine

authors

Ma XJ,Patel R,Wang X,Salunga R,Murage J,Desai R,Tuggle JT,Wang W,Chu S,Stecker K,Raja R,Robin H,Moore M,Baunoch D,Sgroi D,Erlander M

doi

10.1043/1543-2165(2006)130[465:MCOHCU]2.0.CO;2

subject

Has Abstract

pub_date

2006-04-01 00:00:00

pages

465-73

issue

eissn

0003-9985

issn

1543-2165

pii

OA51149

journal_volume

130

pub_type

杂志文章

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Molecular classification of human cancers using a 92-gene real-time quantitative polymerase chain reaction assay.